s-triazine-based Derivatives as Anticancer Agents

Heterocyclic derivatives represent the primary scaffold for numerous medicinal agents of utmost importance for humanity. Among them, triazine derivatives, and particularly the s-triazine scaffold, have long represented a cornerstone in medicinal chemistry research due to their broad pharmacological versatility. This heterocyclic system is a key structure in the design of therapeutic agents exhibiting antitrypanosomal, antiviral, antimicrobial, anti-inflammatory, antidiabetic, and anticancer activities. The s-triazine core represents a privileged scaffold, allowing rational optimization through targeted substitution patterns at different positions. Indeed, the triazine ring is characterized by the replacement of 3 carbon atoms of a benzene ring with three nitrogens, affording three easily modified sites at positions 2, 4, and 6, which can be variously substituted to modulate physiological and biological activities. In this review, we will focus on the structural and pharmacological features of s-triazine-based compounds developed as anticancer agents. Indeed, cancer is an increasing worldwide emergency, and its incidence and mortality will double in the next twenty years. Thus, the development of innovative and powerful anticancer agents remains one of the biggest challenges in the research world. In this respect, we provide an overview of the recent primary literature concerning the development of s-triazine-based antitumor agents, focusing on the most potent compounds acting on specific molecular targets and discussing the structure-activity relationships (SARs), when available. The aim is to provide important principles for the future development of new anticancer agents with greater potency against drug-sensitive and drug-resistant cancers.